Abstract
Carbohydrate and protein metabolism are often impaired during uremia. We hypothesize this results from some imbalance of positive and/or negative effectors of key enzymes which regulate these pathways, rather than from uremic “toxins”. To test this hypothesis, the effects of hemodialysis on cell metabolism in uremic patients was measured using the circulating neutrophil as a cell model. 60 paired studies have been completed. A 6 hour hemodialysis period was associated with significant (p<0.05) increases in the activities of the regulatory glycolytic enzymes in leukocytes: glucose-6-phosphate dehydrogenase, phosphofructokinase (PFK) & pyruvate kinase (PK). Nucleotide energy charge was correlated with PFK & PK. An accumulation of triosephosphates at the level of the PFK-catalyzed step was noted. Protein synthesis (3H-leucine) increased (p<0.05), while RNA synthesis fell slightly. Cellular concentrations of 13 free amino acids increased. 7 patients with predialysis hyperglycemia (m=160 mg/dl) had increased leukocyte PFK & protein synthesis, with decreased blood glucose, postdialysis. This did not occur in normoglycemic patients. The removal of a dialyzable uremic toxin should have affected cell metabolism in both groups equally. Thus a reversible defect of regulatory enzyme activities in glycolytic and protein synthesis pathways is evident in uremics with carbohydrate intolerance, consistent with some imbalance of metabolic effectors regulating key enzymes.
Supported by Eaton Laboratories, Norwich, N.Y.
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Metcoff, J., Lindeman, R. & Baxter, D. CELL METABOLISM IN UREMIA. Pediatr Res 11, 554 (1977). https://doi.org/10.1203/00006450-197704000-01107
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DOI: https://doi.org/10.1203/00006450-197704000-01107
